Assay Development & Screening Technology (ADST) is designed to advance therapeutic development through research and development of innovative assay (test) designs and chemical library screening methods. Conformational diseases are a group of disorders caused by the misfolding of newly synthesized proteins and subversion of systems that facilitate protein conformational maturation, intracellular trafficking, and proteolysis. They include Alzheimers Disease, Cystic Fibrosis, Type 2 Diabetes, and Alpha-1 antitrypsin (AAT) deficiency. AAT is a genetic condition that is passed from parents to their children through their genes. People with Alpha-1 have received two abnormal alpha-1 antitrypsin genes. The latter disorder is caused by the misfolding of an inherited mutant AAT monomer in the endoplasmic reticulum of hepatocytes. The misfolded monomer is degraded by proteasomes, but can form toxic polymers that are removed by autophagy, and stressed hepatocytes are known to undergo apoptosis. The impaired secretion of AAT can result in serious lung disease in adults (loss of function), whereas the accumulation of toxic polymers in hepatocytes can lead to the development of liver disease at any age (gain of toxic function). Importantly there is extensive phenotypic variability, implicating roles for genetic and/or environmental modifiers. With financial support from The Alpha-1 Project (TAP) and in collaboration with Alpha-1 Foundation scientific advisors we are designing bioassays to discover and develop new therapeutic interventions for AAT deficiency, which may provide general strategies to treat additional conformational disorders.